title: The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense.
abstract: Trypanosoma brucei gambiense causes 97% of all cases of African sleeping sickness, a fatal disease of sub-Saharan Africa. Most species of trypanosome, such as T. b. brucei, are unable to infect humans due to the trypanolytic serum protein apolipoprotein-L1 (APOL1) delivered via two trypanosome lytic factors (TLF-1 and TLF-2). Understanding how T. b. gambiense overcomes these factors and infects humans is of major importance in the fight against this disease. Previous work indicated that a failure to take up TLF-1 in T. b. gambiense contributes to resistance to TLF-1, although another mechanism is required to overcome TLF-2. Here, we have examined a T. b. gambiense specific gene, TgsGP, which had previously been suggested, but not shown, to be involved in serum resistance. We show that TgsGP is essential for resistance to lysis as deletion of TgsGP in T. b. gambiense renders the parasites sensitive to human serum and recombinant APOL1. Deletion of TgsGP in T. b. gambiense modified to uptake TLF-1 showed sensitivity to TLF-1, APOL1 and human serum. Reintroducing TgsGP into knockout parasite lines restored resistance. We conclude that TgsGP is essential for human serum resistance in T. b. gambiense.
authors.affiliation: Wellcome Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Capewell
authors.forename: Caroline
authors.initials: C
authors.lastname: Clucas
authors.forename: Eric
authors.initials: E
authors.lastname: DeJesus
authors.forename: Rudo
authors.initials: R
authors.lastname: Kieft
authors.forename: Stephen
authors.initials: S
authors.lastname: Hajduk
authors.forename: Nicola
authors.initials: N
authors.lastname: Veitch
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Steketee
authors.forename: Anneli
authors.initials: A
authors.lastname: Cooper
authors.forename: William
authors.initials: W
authors.lastname: Weir
authors.forename: Annette
authors.initials: A
authors.lastname: MacLeod
mesh_terms: D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014347:Trypanosoma brucei gambiense / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014353:Trypanosomiasis, African / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D015800:Protozoan Proteins